P1214: SUBCUTANEOUS EPCORITAMAB + R-CHOP FOR FIRST-LINE TREATMENT OF PATIENTS WITH HIGH-RISK DIFFUSE LARGE B-CELL LYMPHOMA: PHASE 1/2 UPDATE
Authors: M. R. Clausen, F. Offner, D. Belada, J. Brody, K. M. Linton, Y. Karimi, R. Cordoba, S. Snauwaert, A. Abbas, L. Wang, J. Wu, B. Elliott, L. Falchi
Journal: HemaSphere (2022)

Background: Patients (pts) with newly diagnosed diffuse large B-cell lymphoma (DLBCL) with high/poor risk according to the revised International Prognostic Index (IPI) who are treated with immunochemotherapy (IC) have a 4-y survival rate of 55% (Sehn et al, Blood 2007). Epcoritamab is a subcutaneously administered, well-tolerated, bispecific antibody with single-agent antitumor activity in relapsed/refractory (R/R) aggressive B-cell non-Hodgkin lymphoma (NHL). As its mechanism of action and safety profile are distinct from IC, epcoritamab is well suited for use in combination therapy and in earlier lines of therapy. The suboptimal prognosis of high-risk pts may be improved with the addition of a novel agent to standard IC. Aims: To present updated results of epcoritamab + rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in previously untreated pts with DLBCL and IPI 3–5 (EPCORE NHL-2 arm 1; NCT04663347). Methods: Adult pts with previously untreated CD20+ DLBCL (IPI ≥3) received subcutaneously administered epcoritamab (every wk, cycles 1–4; every 3 wk, cycles 5–6) + R-CHOP for 6 cycles of 21 d, followed by epcoritamab monotherapy (every 4 wk, in cycles of 28 d, up to 1 y). Corticosteroid prophylaxis and step-up dosing of epcoritamab were required in cycle 1 to mitigate CRS. PET-CT with contrast was used to assess response per Lugano 2014 criteria. Informed consent was obtained. Results: As of the data cutoff date of December 1, 2021, 33 pts had received epcoritamab + R-CHOP (epcoritamab 24 mg, n=4; 48 mg, n=29). Median age was 66 y (range, 19–82); median time from diagnosis to first dose of epcoritamab was 25 d (range, 5–70). At least 24% of pts had double- or triple-hit DLBCL; all had IPI ≥3. Median number of total cycles initiated was 5 (range, 1–13), and median follow-up was 3 mo (0–9.7). Among the 33 pts enrolled, 31 (94%) remained on treatment. The most common treatment-emergent adverse events (TEAEs) were neutropenia (48%; febrile neutropenia in 9% of all pts), CRS (45%), infections (42%), anemia (39%), injection-site reactions (36%), nausea (33%), constipation (30%), and pyrexia (30%). No pts discontinued epcoritamab due to TEAEs. AEs of special interest were CRS (24% grade [G] 1, 18% G2, 3% G3; resolved) and ICANS (3% G2; resolved); tumor lysis syndrome was observed in 1 pt (3% G3). Most CRS events were associated with the first full dose. Median time to resolution of CRS events was 2 d (range, 1–11); 4 pts with CRS were treated with tocilizumab. Epcoritamab was not discontinued or delayed due to CRS. There were no fatal TEAEs. Individual pt response profiles are shown in Figure 1. For efficacy-evaluable pts, irrespective of whether they had yet completed 6 cycles of therapy, the overall response rate (ORR) was 96% (24/25). Among the 10 pts who completed 6 cycles of R-CHOP and had a subsequent response assessment, the ORR and complete metabolic response (CMR) rate were 100% and 90%, respectively. These 10 pts remained in response as of the data cutoff date. The longest duration of response was 7.1+ mo and ongoing. Image:Summary/Conclusion: Epcoritamab is the first subcutaneously administered bispecific antibody to be evaluated in combination with standard IC in pts with previously untreated DLBCL. These results show that epcoritamab + R-CHOP has a manageable safety profile. CRS events were observed to be mostly of low grade and were not associated with treatment discontinuation. Rates of overall response and CMR were high, and no relapses were reported as of the data cutoff date. Updated data will be presented at the meeting.